Life Sciences Commons^™

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

Animal tests yield misleading results.

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Andrew Knight, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Andrew Knight, Ph.D.

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …

Variation In Avian Pathogenic Escherichia Coli Colonization Levels In Chickens, Melissa Monson, Michael Kaiser, Susan Lamont

Melissa Monson

Colonization levels in five tissues after avian pathogenic Escherichia coli (APEC) inoculation were investigated in chickens to generate phenotypic data for a genome wide association study (GWAS). Bacterial loads were measured in 370 birds and varied among individuals and tissues. Mean bacterial levels were significantly different between tissues (right lung > spleen > left lung and liver > blood). There were also significant correlations in bacterial load between tissues. These data suggest that colonization levels could be used as phenotypes in GWAS and could help identify markers associated with poultry resistance to APEC infections. After verification, these markers could be used for genetic …

Association Of Different Iowa Livestock Truck Wash Stations Service Levels With Enterobacteriaceae Counts, Amber Danielson, Samaneh Azarpajouh, Anna Johnson, James Dickson, Locke Karriker, Rodney Baker, Christopher Rademacher, Troy Bigelow, Kenneth Stalder

Samaneh Azarpajouh

Data from eighteen different truck washes were used to compare the association of different service levels with Enterobacteriaceae counts. Service levels were classified into three different categories; prewash (n=78), post wash with disinfectant (n=78), and post wash without disinfectant (n=12). A total of 168 drag swabs were used for collection for the purpose of this study. Prewash services were defined as trailers before they were scraped out and washed. Post wash with or without disinfectant services were defined as after the trailers were washed and disinfectant was or was not applied. Prewash trailers tended to have higher Enterobacteriaceae counts of …

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. …

Recombinant Aav-Mediated Best1 Transfer To The Retinal Pigment Epithelium: Analysis Of Serotype-Dependent Retinal Effects, Karina E. Guziewicz, Barbara Zangerl, András M. Komáromy, Simone Iwabe, Vincent A. Chiodo, Sanford L. Boye, William W. Hauswirth, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr), recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In …

Disease Will Limit Future Food Supply From The Global Crustacean Fishery And Aquaculture Sectors, G. Stentiford, D. Neil, E. Peeler, J. Shields, H. Small, T. Flegel, J. Vlak, B. Jones, F. Morado, S. Moss, J. Lotz, Lyric Bartholomay, D. Behringer, C. Hauton, D. Lightner

Lyric Bartholomay

Seafood is a highly traded food commodity. Farmed and captured crustaceans contribute a significant proportion with annual production exceeding 10 M metric tonnes with first sale value of $40bn. The sector is dominated by farmed tropical marine shrimp, the fastest growing sector of the global aquaculture industry. It is significant in supporting rural livelihoods and alleviating poverty in producing nations within Asia and Latin America while forming an increasing contribution to aquatic food supply in more developed countries. Nations with marine borders often also support important marine fisheries for crustaceans that are regionally traded as live animals and commodity products. …

Psychology And Its Animal Subjects, Kenneth J. Shapiro

Kenneth J. Shapiro, PhD

By way of introducing Psychologists for the Ethical Treatment of Animals (PsyETA) to readers of the journal, I have been asked to make some comments about the organization and, from a personal point of view, to suggest some of my own positions and views.

Three Rs Approaches In The Production And Quality Control Of Fish Vaccines, Paul J. Midtlyng, Coenraad F.M. Hendriksen, Elisabeth Balks, Lukas Bruckner, Lawrence Elsken, Øystein Evensen, Kjetil Fyrand, Allison Guy, Marlies Halder, Penny Hawkins, Gunn Kisen, Anne Berit Romstad, Kira Salonius, Patrick Smith, Lynne U. Sneddon

Lynne Sneddon, PhD

The workshop on Three Rs Approaches in the Production and Quality Control of Fish Vaccines aimed a) to identify animal tests currently stipulated for the production and quality control of fish vaccines and to highlight animal welfare concerns associated with these tests; b) to identify viable options to replace, reduce, and refine animal use for fish vaccine testing; and c) to discuss the way forward and set out how the Three Rs may be implemented without jeopardizing the quality of the vaccines. The workshop participants -- experts from academia, regulatory authorities, a scientific animal welfare organization, and the fish vaccine …

Characterisation Of Chemosensory Trigeminal Receptors In The Rainbow Trout, Oncorhynchus Mykiss: Responses To Chemical Irritants And Carbon Dioxide, Jessica J. Mettam, Catherine R. Mccrohan, Lynne U. Sneddon

Lynne Sneddon, PhD

Trigeminally innervated, mechanically sensitive chemoreceptors (M) were previously identified in rainbow trout, Oncorhynchus mykiss, but it is not known whether these receptors are responsive only to noxious, chemical irritants or have a general chemosensory function. This study aimed to characterise the stimulus–response properties of these receptors in comparison with polymodal nociceptors (P). Both P and M gave similar response profiles to acetic acid concentrations. The electrophysiological properties were similar between the two different afferent types. To determine whether the receptors have a nociceptive function, a range of chemical stimulants was applied to these receptors, including non-noxious stimuli such as ammonium …

Clinical Anesthesia And Analgesia In Fish, Lynne U. Sneddon

Lynne Sneddon, PhD

Fish have become a popular experimental model and companion animal, and are also farmed and caught for food. Thus, surgical and invasive procedures in this animal group are common, and this review will focus on the anesthesia and analgesia of fish. A variety of anesthetic agents are commonly applied to fish via immersion. Correct dosing can result in effective anesthesia for acute procedures as well as loss of consciousness for surgical interventions. Dose and anesthetic agent vary between species of fish and are further confounded by a variety of physiological parameters (e.g., body weight, physiological stress) as well as environmental …

The Efficacy Of Three Types Of Analgesic Drugs In Reducing Pain In The Rainbow Trout, Oncorhynchus Mykiss, Jessica J. Mettam, Lois J. Oulton, Catherine R. Mccrohan, Lynne U. Sneddon

Lynne Sneddon, PhD

Recent research has shown the possibility of pain perception in fish; therefore, the use of analgesia or “painkillers” should be considered for invasive procedures. However, there is relatively little information on the effectiveness of analgesic drugs nor on the appropriate dose for fish. This study assessed the efficacy of three types of drug: an opioid, buprenorphine, a non-steroidal anti-inflammatory drug (NSAID), carprofen and a local anaesthetic, lidocaine. Each drug was tested at three doses on rainbow trout that were noxiously stimulated and the most effective dose was also given to fish experiencing no pain to investigate side-effects. Ventilation rate and …

Diffusion Tensor Imaging Of Dolphin Brains Reveals Direct Auditory Pathway To Temporal Lobe, Gregory S. Berns, Peter F. Cook, Sean Foxley, Saad Jbabdi, Karla L. Miller, Lori Marino

Lori Marino, Ph.D.

The brains of odontocetes (toothed whales) look grossly different from their terrestrial relatives. Because of their adaptation to the aquatic environment and their reliance on echolocation, the odontocetes’ auditory system is both unique and crucial to their survival. Yet, scant data exist about the functional organization of the cetacean auditory system. A predominant hypothesis is that the primary auditory cortex lies in the suprasylvian gyrus along the vertex of the hemispheres, with this position induced by expansion of ‘associative0 regions in lateral and caudal directions. However, the precise location of the auditory cortex and its connections are still unknown. Here, …

Free-Roaming Dogs In Developing Countries: The Benefits Of Capture, Neuter, And Return Programs, Jennifer Jackman, Andrew N. Rowan

Jennifer Jackman, Ph.D.

This chapter provides an overview of animal welfare and public health problems associated with free-roaming dog populations and strategies to resolve these problems. Placing CNR programs in the context of earlier dog and rabies control methods, the chapter explores CNR’s potential to overcome some of the shortcomings of earlier approaches and to improve animal welfare, reduce dog population growth, and prevent the spread of rabies and other canine-transmitted diseases. Constraints and current debates on current implementation of CNR programs are also examined.

Relative Volume Of The Cerebellum In Dolphins And Comparison With Anthropoid Primates, L. Marino, James K. Rilling, Shinko K. Lin, Sam H. Ridgway

Lori Marino, PhD

According to the ‘developmental constraint hypothesis’ of comparative mammalian neuroanatomy, brain growth follows predictable allometric trends. Therefore, brain structures should scale to the entire brain in the same way across mammals. Evidence for a departure from this pattern for cerebellum volume has recently been reported among the anthropoid primates. One of the mammalian groups that has been neglected in tests of the ‘developmental constraint hypothesis’ is the cetaceans (dolphins, whales, and porpoises). Because many cetaceans possess relative brain sizes in the range of primates comparative tests of the ‘developmental constraint hypothesis’ across these two groups could help to delineate the …

The Evolutionary History Of Cetacean Brain And Body Size, Stephen H. Montgomery, Jonathan H. Geisler, Michael R. Mcgowen, Charlotte Fox, Lori Marino, John Gatesy

Lori Marino, PhD

Cetaceans rival primates in brain size relative to body size and include species with the largest brains and biggest bodies to have ever evolved. Cetaceans are remarkably diverse, varying in both phenotypes by several orders of magnitude, with notable differences between the two extant suborders, Mysticeti and Odontoceti.We analyzed the evolutionary history of brain and body mass, and relative brain size measured by the encephalization quotient (EQ), using a data set of extinct and extant taxa to capture temporal variation in the mode and direction of evolution. Our results suggest that cetacean brain and body mass evolved under strong directional …

Physiological And Behavioural Responses To Noxious Stimuli In The Atlantic Cod (Gadus Morhua), Jared R. Eckroth, Øyvind Aas-Hansen, Lynne U. Sneddon, Helena Bichão, Kjell B. Døving

Lynne Sneddon, PhD

In the present study, our aim was to compare physiological and behavioural responses to different noxious stimuli to those of a standardized innocuous stimulus, to possibly identify aversive responses indicative of injury detection in a commercially important marine teleost fish, the Atlantic cod. Individual fish were administered with a noxious stimulus to the lip under short-term general anaesthesia (MS-222). The noxious treatments included injection of 0.1% or 2% acetic acid, 0.005% or 0.1% capsaicin, or piercing the lip with a commercial fishing hook. Counts of opercular beat rate (OBR) at 10, 30, 60, 90 and 120 min and observations of …

The Harmful, Nontherapeutic Use Of Animals In Research Is Morally Wrong, Nathan Nobis

Nathan M. Nobis, PhD

It is argued that using animals in research is morally wrong when the research is nontherapeutic and harmful to the animals. This article discusses methods of moral reasoning and discusses how arguments on this and other bioethical issues might be defended and critiqued. A basic method of moral argument analysis is presented and used to show that common objections to the view that “animal research is morally wrong” fail: ie, common arguments for the view that “animal research is morally permissible” are demonstrably unsound or in need of defense. It is argued that the best explanations why harmful, nontherapeutic research …

Interests And Harms In Primate Research, Nathan Nobis

Nathan M. Nobis, PhD

The article discusses the moral issues on primate research in reference to the moral defenses by Sughrue and colleagues. It states that Sughrue and colleagues have claimed to provide equal examination of the primate stroke research's ethics. It mentions that the promise to straighten out a number of ethical arguments in favor and against primate research was not fulfilled. Several moral arguments are presented in response to Sughrue and colleagues' moral defense for animal experimentation.

Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens

Andrew N. Rowan, DPhil

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation.

This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress …

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Andrew N. Rowan, DPhil

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress …

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Andrew N. Rowan, DPhil

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet …

Effects Of Forage Quality, Mdgs, And Monensin On Performance, Methane Concentration, And Ruminal Fermentation Of Growing Cattle, Anna C. Pesta, Andrea K. Watson, Samodha Fernando, Galen E. Erickson

Samodha C. Fernando

A growing study was conducted to evaluate a novel method for measuring methane concentration by feedlot cattle, and to determine the effects of forage quality, inclusion of modified distillers grains plus solubles (MDGS), and presence or absence of monensin on performance, methane concentration, and rumen fermentation characteristics. Performance was improved by use of high-quality forage and MDGS, while response to monensin was variable across basal diet type. Response of methane concentration and volatile fatty acid (VFA) profile due to diet was variable and subject to multiple interactions, reflecting the complexity of the microbial processes involved within the rumen.

Differences In Fecal Bacterial Community Composition Between Beef Steers Which Are High-Shedders And Low-Shedders Of Shiga Toxin-Producing Escherichia Coli (Stec), Nirosh D. Aluthge, Yoshitha A. Wanniarachchi, Brandon L. Nuttelman, Cody J. Schneider, Terry J. Klopfenstein, Galen E. Erickson, Samodha C. Fernando

Samodha C. Fernando

The community composition of the fecal microbiota was compared between beef steers which were high-shedders and low-shedders of Shiga toxin-producing Escherichia coli. Based on Shannon and Chao 1 diversity indices, the high-shedders had a more diverse fecal bacterial community than the low-shedding steers. Members of the genus Prevotella were observed as being more abundant in the low-shedders compared to the high-shedders, while Succinivibrio were more abundant in the high-shedders. Isolation of specific bacteria which are significantly more abundant in low-shedders may pave the way to developing direct-fed microbials which are effective in reducing STEC shedding among high-shedding beef steers.

Repeated Stressors In Adulthood Increase The Rate Of Biological Ageing, Michaela Hau, Mark F. Haussmann, Timothy J. Greives, Christa Matlack, David Costantini, Michael Quetting, James S. Adelman, Ana C. Miranda, Jesko Partecke

James S. Adelman

Individuals of the same age can differ substantially in the degree to which they have accumulated tissue damage, akin to bodily wear and tear, from past experiences. This accumulated tissue damage reflects the individual’s biological age and may better predict physiological and behavioural performance than the individual‘s chronological age. However, at present it remains unclear how to reliably assess biological age in individual wild vertebrates. We exposed hand-raised adult Eurasian blackbirds (Turdus merula) to a combination of repeated immune and disturbance stressors for over one year to determine the effects of chronic stress on potential biomarkers of biological ageing including …

Examining The Regulatory Value Of Multi-Route Mammalian Acute Systemic Toxicity Studies, Troy Seidle, Pilar Prieto, Anna Bulgheroni

Troy Seidle, PhD

Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oralinhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure active substances were more severe than those derived from dermal data in more than …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …